Department of Cell Physiology & Metabolism, University of Geneva Faculty of Medicine, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland.
Nature. 2010 Apr 22;464(7292):1149-54. doi: 10.1038/nature08894. Epub 2010 Apr 4.
Pancreatic insulin-producing beta-cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, beta-cell loss). It is not known whether adult mammals can differentiate (regenerate) new beta-cells after extreme, total beta-cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-beta-cell) source. Here we show beta-cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-total beta-cell ablation. If given insulin, the mice survived and showed beta-cell mass augmentation with time. Lineage-tracing to label the glucagon-producing alpha-cells before beta-cell ablation tracked large fractions of regenerated beta-cells as deriving from alpha-cells, revealing a previously disregarded degree of pancreatic cell plasticity. Such inter-endocrine spontaneous adult cell conversion could be harnessed towards methods of producing beta-cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration.
胰腺胰岛素分泌β细胞寿命长，因此在健康条件下，它们在一生中很少进行复制。然而，在代谢需求增加或损伤后（即β细胞损失），它们表现出自我复制增加。目前尚不清楚成年哺乳动物在极度、完全的β细胞损失（如糖尿病）后是否能够分化（再生）新的β细胞。这表明分化来自前体细胞或另一种异源（非β细胞）来源。在这里，我们在白喉毒素诱导的急性选择性近完全β细胞消融的转基因模型中显示了β细胞再生。如果给予胰岛素，小鼠存活下来，并且随着时间的推移β细胞质量增加。在β细胞消融之前用谱系追踪标记产生胰高血糖素的α细胞，追踪到大量再生β细胞来源于α细胞，揭示了以前被忽视的胰腺细胞可塑性程度。这种内分泌间的自发成年细胞转换可以被用于产生用于糖尿病治疗的β细胞的方法，无论是在体外的分化环境中还是在诱导的再生中。
